The aim of this proposal is to determine the causes and cellular mechanisms responsible for increased sensitivity of cerebral blood vessels chronically exposed to extraluminal blood. Two methods will be used for chronic exposure of rabbit basilar arteries to blood. Blood will be injected into the subarachnoid space of rabbits to simulate subarachnoid hemorrhage. Rabbit basilar arteries will also be implanted in the anterior eye chamber of host animals and the implants exposed to blood by blood injections into the anterior chamber containing the implant. In vitro dose-response curves for vasoconstrictors and vasodilators and the response to nerve stimulation will be compared in blood-free and blood-exposed arterial segments. Intracelluar membrane potential will be recorded and calcium dependent electrical spike activity analyzed in control and blood-exposed cerebral vessels. These techiques will be used in experiments designed to determine the causes and mechanisms of blood-induced supersensitivity of rabbit basilar arteries. The time course for development of supersensitivity will be described to determine the time for onset of the phenomenon and whether it is transient or maintained. Sympathetically denervated cerebral arteries exposed to blood will be used to separate direct effects of blood on vascular muscle sensitivity from indirect blood-induced sympathetic denervation effects on vascular muscle. A possible reduced relaxation response of blood-exposed arteries to vasodilators will also be investigated. The cellular mechanisms responsible for altered vascular reactivity will also be studied. Membrane depolarization and the effects of ouabain on electrical and mechanical activity will be investigated to explore the role of inhibition of the vascular Na+ K+ pump as a cause of blood-induced supersensitivity. Alterations in calcium movements will be examined by measuring electrically induced spike activity in the presence of tetraethylammonium. Arteries implanted in the anterior eye chamber and exposed to blood will be studied so that eventaully human cerebral arteries can be implanted and effects of blood investigated. It is hoped that a better understanding of the effects of blood on cerebral arteries will lead to more effective therapy for blood-induced cerebrovasospasm.